Hemerythrin-like domain of FBXL5-like proteins; Human FBXL5 (F-box and leucine-rich repeat protein 5) protein plays a role in cellular iron homeostasis. It is part of an E3 ubiquitin ligase complex that targets the iron regulatory protein IRP2 for proteasomal degradation. The FBXL5's stability is regulated by iron concentration, with its iron- and oxygen-binding hemerythrin domain acting as a ligand-dependent regulatory switch.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 302129687   7 EVDVFTAPHWRMKQLVGLYCDKLSKTNFSNNNDFRALLQSLYATFKEFKMHEQIENEYIIGLLQQRSQT----IYNVHSD 82
Cdd:cd12109    1 RVDVYGFIHKALRALLFDLLQKLGRTDFSDPQDLAALLESLRRLLQEFKAHEQHENEFIHPLLEKRLPGlsaaVANEHSD 80

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 302129687  83 NKLSEMLSLFEKGLKNVKNEYEQLNYAKQLKERLEAFTRDFLPHMKEEEEVFQPMLMEYFTYEELKDIKKKVIAQHCS 160
Cdd:cd12109   81 HDLSIMLLLELLGALRTAPEAERPAAGRQLYRALAAFVADNLPHMHEEETVFQPLLWEYFSDEELKAIKKAVIASHPP 158

Antagonist of mitotic exit network protein 1; Amn1 has been functionally characterized in Saccharomyces cerevisiae as a component of the Antagonist of MEN pathway (AMEN). The AMEN network is activated by MEN (mitotic exit network) via an active Cdc14, and in turn switches off MEN. Amn1 constitutes one of the alternative mechanisms by which MEN may be disrupted. Specifically, Amn1 binds Tem1 (Termination of M-phase, a GTPase that belongs to the RAS superfamily), and disrupts its association with Cdc15, the primary downstream target. Amn1 is a leucine-rich repeat (LRR) protein, with 12 repeats in the S. cerevisiae ortholog. As a negative regulator of the signal transduction pathway MEN, overexpression of AMN1 slows the growth of wild type cells. The function of the vertebrate members of this family has not been determined experimentally, they have fewer LRRs that determine the extent of this model.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 302129687 353 LCPNLEHLDLTQTDISDSAFDswsWLGCCQSLRHLDLSGCEKITDVALEKISRAL 407
Cdd:cd09293   26 LHSGLEWLELYMCPISDPPLD---QLSNCNKLKKLILPGSKLIDDEGLIALAQSC 77

Hemerythrin-like domain of FBXL5-like proteins; Human FBXL5 (F-box and leucine-rich repeat protein 5) protein plays a role in cellular iron homeostasis. It is part of an E3 ubiquitin ligase complex that targets the iron regulatory protein IRP2 for proteasomal degradation. The FBXL5's stability is regulated by iron concentration, with its iron- and oxygen-binding hemerythrin domain acting as a ligand-dependent regulatory switch.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 302129687   7 EVDVFTAPHWRMKQLVGLYCDKLSKTNFSNNNDFRALLQSLYATFKEFKMHEQIENEYIIGLLQQRSQT----IYNVHSD 82
Cdd:cd12109    1 RVDVYGFIHKALRALLFDLLQKLGRTDFSDPQDLAALLESLRRLLQEFKAHEQHENEFIHPLLEKRLPGlsaaVANEHSD 80

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 302129687  83 NKLSEMLSLFEKGLKNVKNEYEQLNYAKQLKERLEAFTRDFLPHMKEEEEVFQPMLMEYFTYEELKDIKKKVIAQHCS 160
Cdd:cd12109   81 HDLSIMLLLELLGALRTAPEAERPAAGRQLYRALAAFVADNLPHMHEEETVFQPLLWEYFSDEELKAIKKAVIASHPP 158

F-box-like; This is an F-box-like family.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 302129687  204 ITHLPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTKTGSLWKHLY 248
Cdd:pfam12937   1 LSSLPDEILLQIFSYLDPKDLLRLALVCRRWRELASDDSLWRRLC 45

A Receptor for Ubiquitination Targets;

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|.
gi 302129687   207 LPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTKTGSLWKHL 247
Cdd:smart00256   1 LPDEILEEILSKLDPKDLLRLRKVSRKWRSLIDSHDFWFKL 41

Leucine-rich repeat - CC (cysteine-containing) subfamily;

                           10        20
                   ....*....|....*....|....*
gi 302129687   381 CQSLRHLDLSGCEKITDVALEKISR 405
Cdd:smart00367   1 CPNLRELDLSGCTNITDEGLQALAK 25

Antagonist of mitotic exit network protein 1; Amn1 has been functionally characterized in Saccharomyces cerevisiae as a component of the Antagonist of MEN pathway (AMEN). The AMEN network is activated by MEN (mitotic exit network) via an active Cdc14, and in turn switches off MEN. Amn1 constitutes one of the alternative mechanisms by which MEN may be disrupted. Specifically, Amn1 binds Tem1 (Termination of M-phase, a GTPase that belongs to the RAS superfamily), and disrupts its association with Cdc15, the primary downstream target. Amn1 is a leucine-rich repeat (LRR) protein, with 12 repeats in the S. cerevisiae ortholog. As a negative regulator of the signal transduction pathway MEN, overexpression of AMN1 slows the growth of wild type cells. The function of the vertebrate members of this family has not been determined experimentally, they have fewer LRRs that determine the extent of this model.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 302129687 602 LSLSGCYQITDHGLRVLTLGggLPYLEHLNLSGCLTITGAGLQDLVSACPSL 653
Cdd:cd09293   57 LILPGSKLIDDEGLIALAQS--CPNLQVLDLRACENITDSGIVALATNCPKL 106

Hemerythrin-like domain of FBXL5-like proteins; Human FBXL5 (F-box and leucine-rich repeat protein 5) protein plays a role in cellular iron homeostasis. It is part of an E3 ubiquitin ligase complex that targets the iron regulatory protein IRP2 for proteasomal degradation. The FBXL5's stability is regulated by iron concentration, with its iron- and oxygen-binding hemerythrin domain acting as a ligand-dependent regulatory switch.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 302129687   7 EVDVFTAPHWRMKQLVGLYCDKLSKTNFSNNNDFRALLQSLYATFKEFKMHEQIENEYIIGLLQQRSQT----IYNVHSD 82
Cdd:cd12109    1 RVDVYGFIHKALRALLFDLLQKLGRTDFSDPQDLAALLESLRRLLQEFKAHEQHENEFIHPLLEKRLPGlsaaVANEHSD 80

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 302129687  83 NKLSEMLSLFEKGLKNVKNEYEQLNYAKQLKERLEAFTRDFLPHMKEEEEVFQPMLMEYFTYEELKDIKKKVIAQHCS 160
Cdd:cd12109   81 HDLSIMLLLELLGALRTAPEAERPAAGRQLYRALAAFVADNLPHMHEEETVFQPLLWEYFSDEELKAIKKAVIASHPP 158

F-box domain found in F-box/LRR-repeat protein 5 (FBXL5) and similar proteins; FBXL5, also called F-box and leucine-rich repeat protein 5, F-box protein FBL4/FBL5, or p45SKP2-like protein, is the substrate-recognition component of an SCF (SKP1-cullin-F-box) protein ligase complex that plays a central role in iron homeostasis by promoting the ubiquitination and subsequent degradation of IREB2/IRP2. The F-box domain has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|.
gi 302129687 204 ITHLPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTKTGSLW 244
Cdd:cd22118    1 ISSLPPEIMLKIFSYLNPQDLCRCAQVCTKWSQLARDGSLW 41

F-box-like; This is an F-box-like family.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 302129687  204 ITHLPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTKTGSLWKHLY 248
Cdd:pfam12937   1 LSSLPDEILLQIFSYLDPKDLLRLALVCRRWRELASDDSLWRRLC 45

F-box domain found in F-box only protein 11 (FBXO11) and similar proteins; FBXO11, also called FBX11, protein arginine N-methyltransferase 9 (PRMT9), or vitiligo-associated protein 1 (VIT-1), is the substrate-recognition component of an SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins, such as DTL/CDT2, BCL6 and PRDM1/BLIMP1. The F-box domain has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|...
gi 302129687 206 HLPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTKTGSLWKHLY 248
Cdd:cd22091    3 ELPDEVLLKIFSYLLEQDLCRAAQVCKRFNTLANDPELWKRLY 45

F-box domain found in F-box/LRR-repeat protein 13 (FBXL13) and similar proteins; FBXL13, also called F-box and leucine-rich repeat protein 13, or dynein regulatory complex subunit 6, is a component of the nexin-dynein regulatory complex (N-DRC), a key regulator of ciliary/flagellar motility which maintains the alignment and integrity of the distal axoneme and regulates microtubule sliding in motile axonemes. It is also the substrate-recognition component of an SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex. The F-box domain has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|.
gi 302129687 204 ITHLPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTKTGSLW 244
Cdd:cd22124    1 ISLLPRKAALKIFSYLDLRDLARCAQVCRSWKVITQSSSLW 41

F-box domain; This domain is approximately 50 amino acids long, and is usually found in the N-terminal half of a variety of proteins. Two motifs that are commonly found associated with the F-box domain are the leucine rich repeats (LRRs; pfam00560 and pfam07723) and the WD repeat (pfam00400). The F-box domain has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 302129687  204 ITHLPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTKTGSLWKH 246
Cdd:pfam00646   1 LLDLPDDLLLEILSRLDPKDLLRLSLVSKRWRSLVDSLKLWKK 43

F-box domain found in the JmjC domain-containing histone demethylation protein (JHDM) family; The JHDM family includes F-box/LRR-repeat proteins FBXL10, FBXL11 and FBXL19. FBXL10 is also called lysine-specific demethylase 2B (KDM2B), CXXC-type zinc finger protein 2 (CXXC2), F-box and leucine-rich repeat protein 10 (FBL10), JmjC domain-containing histone demethylation protein 1B (JHDM1B), Jumonji domain-containing EMSY-interactor methyltransferase motif protein, protein JEMMA, protein-containing CXXC domain 2, [Histone-H3]-lysine-36 demethylase 1B, or NDY1. It is a histone demethylase that catalyzes the demethylation of H3K4me3 and H3K36me2, thereby playing a central role in the histone code. It preferentially binds the transcribed region of ribosomal RNA and represses the transcription of ribosomal RNA genes which inhibits cell growth and proliferation. FBXL10 may also serve as the substrate-recognition component of an SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex. FBXL11, also called KDM2A, CXXC8, F-box and leucine-rich repeat protein 11, F-box protein FBL7, F-box protein Lilina, JmjC domain-containing histone demethylation protein 1A (JHDM1A), or [Histone-H3]-lysine-36 demethylase 1A, is a histone H3 lysine 36 (H3K36) demethylase that regulates epithelial mesenchymal transition (EMT) and the metastasis of ovarian cancer. It plays an essential role in embryonic development and homeostasis by regulating cell proliferation and survival. FBXL11 may also recognize and bind to some phosphorylated proteins and promote their ubiquitination and degradation. It associates with centromeres and represses transcription of small non-coding RNAs that are encoded by the clusters of satellite repeats at the centromere. It is required to sustain centromeric integrity and genomic stability, particularly during mitosis. FBXL19, also called F-box and leucine-rich repeat protein 19, is the substrate-recognition component of an SCF-type E3 ubiquitin ligase complex. It acts as a CpG island-binding protein in mouse embryonic stem (ES) cells and has been shown to associate with the CDK-Mediator complex. It promotes H2Bub1 at the promoters of CpG island-containing genes by interacting with RNF20. The F-box domain has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|
gi 302129687 207 LPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTKTGSLWKH 246
Cdd:cd22122    4 LPREVWLPVFQYLSPKDLCVCMRVCKTWNRWCCDPSLWKR 43

F-box domain found in uncharacterized F-box protein group similar to F-box only protein 3 (FBXO3); This subfamily corresponds to a group of uncharacterized F-box proteins which show sequence similarity to F-box only protein 3 (FBXO3). FBXO3, also called FBX3, is the substrate-recognition component of an SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex, that mediates the ubiquitination of HIPK2 and probably that of EP300, leading to rapid degradation by the proteasome. It also promotes ubiquitylation and transcriptional activity of AIRE (autoimmune regulator). The F-box domain has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|.
gi 302129687 207 LPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTKTGSLWKHL 247
Cdd:cd22139    4 LPDELWLHIFSFLSPKDLCQVALVCRRFNRLASDESLWKQI 44

F-box domain found in F-box only protein 3 (FBXO3) and similar proteins; FBXO3, also called FBX3, is the substrate-recognition component of an SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex. It mediates the ubiquitination of HIPK2 and probably that of EP300, leading to rapid degradation by the proteasome. It also promotes ubiquitylation and transcriptional activity of AIRE (autoimmune regulator). The F-box domain has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 302129687 206 HLPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTKTGSLWKHLYPVHW 252
Cdd:cd22084    3 DLPSDPLLNILSFLDYRDLISCSQVCRRLNQLCSHDPLWKRLCKKYW 49

F-box domain found in epithelial cell-transforming sequence 2 oncogene-like (ECT2L) and similar proteins; ECT2L, also called lung-specific F-box and DH domain-containing protein, or putative guanine nucleotide exchange factor LFDH, may act as a guanine nucleotide exchange factor (GEF). The F-box domain has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|
gi 302129687 205 THLPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTKTGSLW 244
Cdd:cd22173    4 TVLPRFLSLYIFSFLDPRSLCRAAQVSWHWKFLAEQDCLW 43

Hemerythrin HHE cation binding domain; Iteration of the HHE family found it to be related to Hemerythrin. It also demonstrated that what has been described as a single domain in fact consists of two cation binding domains. Members of this family occur all across nature and are involved in a variety of processes. For instance, in Nereis diversicolor Swiss:P80255 binds Cadmium so as to protect the organizm from toxicity. However Hemerythrin is classically described as Oxygen-binding through two attached Fe2+ ions. And the bacterial Swiss:Q7WX96 is a regulator of response to NO, which suggests yet another set-up for its metal ligands. In Staphylococcus aureus P72360 has been noted to be important when the organizm switches to living in environments with low oxygen concentrations; perhaps this protein acts as an oxygen store or scavenger. This domain can bind oxygen (Matilla et.al., FEMS Microbiology Reviews, fuab043, 45, 2021, 1. https://doi.org/10.1093/femsre/fuab043)

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 302129687    8 VDVFTAPHWRMKQLVGLYCDKLSKTNFSNNNDFRALLQSLyatFKEFKMHEQIENEYIIGLLQQRS---QTIYNVHSD-- 82
Cdd:pfam01814   3 IELLDAEHRRLRELLALLRALADALGDSHLRKLAELLDEL---VDELEAHHAAEEELLFPALERRSpggEAPIEVLRKeh 79

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 302129687   83 NKLSEMLSLFEKGLKNVKNEYEqlnyakqLKERLEAFTRDFLPHMKEEEEVFQPML 138
Cdd:pfam01814  80 DEIRELLEELEALLKGAEPGAA-------FAELLEALAEWLREHIAKEEEVLFPLL 128

F-box domain found in Saccharomyces cerevisiae cell division control protein 4 (ScCDC4) and similar proteins; ScCDC4 is the substrate-recognition component of an SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. It is essential for initiation of DNA replication and separation of the spindle pole bodies to form the poles of the mitotic spindle. It also plays a role in bud development, fusion of zygotic nuclei after conjugation and various aspects of sporulation. The F-box domain has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....
gi 302129687 204 ITHLPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTKTGSLWKHL 247
Cdd:cd22141    1 IGNLPFEISLKIFNYLQFEDLLNSLGVSKKWNKIIRNTALWKKL 44

F-box domain found in F-box/LRR-repeat protein 12 (FBXL12) and similar proteins; FBXL12, also called F-box and leucine-rich repeat protein 12, or F-box protein FBL12, is the substrate-recognition component of an SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex. It mediates the polyubiquitination and proteasomal degradation of calcium/calmodulin dependent protein kinase I (CAMK1) leading to disruption of cyclin D1/CDK4 complex assembly, which results in G1 cell cycle arrest in lung epithelia. It regulates T-cell differentiation in a cell-autonomous manner. The F-box domain has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|..
gi 302129687 204 ITHLPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTKTGSLWK 245
Cdd:cd22123    1 LDQLPENVLLEILSYLPVRDLLRISRVCKRWRRLVYDKTLWR 42

F-box domain found in F-box/WD repeat-containing protein 2 (FBXW2) and similar proteins; FBXW2, also called F-box and WD-40 domain-containing protein 2, or protein MD6, is the substrate-recognition component of an SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex. It acts as a tumor suppressor by promoting SKP2 degradation. The F-box domain has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression.

                         10        20        30
                 ....*....|....*....|....*....|.
gi 302129687 204 ITHLPPEVMLSIFSYLNPQELCRCSQVSMKW 234
Cdd:cd22131    3 LKLLPLELSFYLLSFLDPESLLTCCLVSKQW 33

F-box domain found in F-box only protein 10 (FBXO10) and similar proteins; FBXO10, also called FBX10, or PRMT11, is the substrate-recognition component of an SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex. The SCF(FBXO10) complex mediates ubiquitination and degradation of BCL2, an anti-apoptotic protein, thereby playing a role in apoptosis by controlling the stability of BCL2. It also associates with the receptor for advanced glycation end products (RAGE) to mediate its ubiquitination and degradation. The F-box domain has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 302129687 204 ITHLPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTKT--GSLWKHLY 248
Cdd:cd22090    2 VTGLPLELWRLILAYLPVRDLCRCCQVCRAWYELILSldSTRWKQLY 48

F-box domain found in F-box only protein 15 (FBXO15) and similar proteins; FBXO15, also called FBX15, has a novel dual molecular function by controlling transcriptional repression and being part of SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligases, which is essential for stress response, gliotoxin production and virulence in the opportunistic human pathogen Aspergillus fumigatus. The F-box domain has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 302129687 204 ITHLPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTKTGSLWKHLY 248
Cdd:cd22093    1 IERLPSEILLKILSYLDASSLLCISCVNKLFYQLANDNALWRKLY 45

Antagonist of mitotic exit network protein 1; Amn1 has been functionally characterized in Saccharomyces cerevisiae as a component of the Antagonist of MEN pathway (AMEN). The AMEN network is activated by MEN (mitotic exit network) via an active Cdc14, and in turn switches off MEN. Amn1 constitutes one of the alternative mechanisms by which MEN may be disrupted. Specifically, Amn1 binds Tem1 (Termination of M-phase, a GTPase that belongs to the RAS superfamily), and disrupts its association with Cdc15, the primary downstream target. Amn1 is a leucine-rich repeat (LRR) protein, with 12 repeats in the S. cerevisiae ortholog. As a negative regulator of the signal transduction pathway MEN, overexpression of AMN1 slows the growth of wild type cells. The function of the vertebrate members of this family has not been determined experimentally, they have fewer LRRs that determine the extent of this model.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 302129687 353 LCPNLEHLDLTQTDISDSAFDswsWLGCCQSLRHLDLSGCEKITDVALEKISRAL 407
Cdd:cd09293   26 LHSGLEWLELYMCPISDPPLD---QLSNCNKLKKLILPGSKLIDDEGLIALAQSC 77

Antagonist of mitotic exit network protein 1; Amn1 has been functionally characterized in Saccharomyces cerevisiae as a component of the Antagonist of MEN pathway (AMEN). The AMEN network is activated by MEN (mitotic exit network) via an active Cdc14, and in turn switches off MEN. Amn1 constitutes one of the alternative mechanisms by which MEN may be disrupted. Specifically, Amn1 binds Tem1 (Termination of M-phase, a GTPase that belongs to the RAS superfamily), and disrupts its association with Cdc15, the primary downstream target. Amn1 is a leucine-rich repeat (LRR) protein, with 12 repeats in the S. cerevisiae ortholog. As a negative regulator of the signal transduction pathway MEN, overexpression of AMN1 slows the growth of wild type cells. The function of the vertebrate members of this family has not been determined experimentally, they have fewer LRRs that determine the extent of this model.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 302129687 339 SSAVSSKMVRQILELCPNLEHLDLTQTDISDSAFDSWSWlGCCQSLRHLDLSGCEKITDVALEKI 403
Cdd:cd09293  117 GHLITDVSLSALGKNCTFLQTVGFAGCDVTDKGVWELAS-GCSKSLERLSLNNCRNLTDQSIPAI 180

F-box domain found in F-box only protein 13 (FBXO13) and similar proteins; FBXO13, also called FBX13, F-box/LRR-repeat protein 17 (FBL17), or F-box and leucine-rich repeat protein 17 (FBXL17), is the substrate-recognition component of SCF(FBXL17) E3 ubiquitin ligase complex, a key component of a quality control pathway required to ensure functional dimerization of BTB domain-containing proteins (dimerization quality control, DQC). The F-box domain has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 302129687 203 GITHLPPEVMLSIFSYLNPQELCR-CSQVSMKWSQLTKTGSLWKHL 247
Cdd:cd22092    1 NINQLPDSILLKIFSYLSLQERCLsASLVCKYWRDLCLDSQFWKQI 46

F-box domain found in F-box/LRR-repeat protein 7 (FBXL7) and similar proteins; FBXL7, also called F-box and leucine-rich repeat protein 7, or F-box protein FBL6/FBL7, is the substrate-recognition component of an SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of Aurora kinase A (AURKA) during mitosis, causing mitotic arrest. The F-box domain has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression.

                         10        20        30
                 ....*....|....*....|....*....|....*...
gi 302129687 207 LPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTKTGSLW 244
Cdd:cd22120    4 LPDDVILQIFSHLPTNQLCRCARVCRRWYNLAWDPRLW 41

Leucine Rich repeats (2 copies); Leucine rich repeats are short sequence motifs present in a number of proteins with diverse functions and cellular locations. These repeats are usually involved in protein-protein interactions. Each Leucine Rich Repeat is composed of a beta-alpha unit. These units form elongated non-globular structures. Leucine Rich Repeats are often flanked by cysteine rich domains.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 302129687  355 PNLEHLDLTQTDISDsafdsWSWLGCCQSLRHLDLSGCEKITDV 398
Cdd:pfam12799   1 PNLEVLDLSNNQITD-----IPPLAKLPNLETLDLSGNNKITDL 39

Antagonist of mitotic exit network protein 1; Amn1 has been functionally characterized in Saccharomyces cerevisiae as a component of the Antagonist of MEN pathway (AMEN). The AMEN network is activated by MEN (mitotic exit network) via an active Cdc14, and in turn switches off MEN. Amn1 constitutes one of the alternative mechanisms by which MEN may be disrupted. Specifically, Amn1 binds Tem1 (Termination of M-phase, a GTPase that belongs to the RAS superfamily), and disrupts its association with Cdc15, the primary downstream target. Amn1 is a leucine-rich repeat (LRR) protein, with 12 repeats in the S. cerevisiae ortholog. As a negative regulator of the signal transduction pathway MEN, overexpression of AMN1 slows the growth of wild type cells. The function of the vertebrate members of this family has not been determined experimentally, they have fewer LRRs that determine the extent of this model.

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                 ....*....|....*....|....*....|....*....|....*....|..
gi 302129687 602 LSLSGCYQITDHGLRVLTLGggLPYLEHLNLSGCLTITGAGLQDLVSACPSL 653
Cdd:cd09293   57 LILPGSKLIDDEGLIALAQS--CPNLQVLDLRACENITDSGIVALATNCPKL 106

F-box domain found in F-box only protein 7 (FBXO7) and similar proteins; FBXO7, also called FBX7, is the substrate-recognition component of an SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. It recognizes BIRC2 and DLGAP5. FBXO7 plays a role downstream of PINK1 in the clearance of damaged mitochondria via selective autophagy (mitophagy) by targeting PRKN to dysfunctional depolarized mitochondria. It promotes MFN1 ubiquitination. FBXO7 acts as a cell cycle regulator by enhancing cyclin D/cyclin-dependent kinase 6 (Cdk6) complex formation and stabilizing levels of p27, a cyclin-dependent kinase inhibitor. Mutations in the FBXO7 (PARK15) gene have been implicated in a juvenile form of parkinsonism called parkinsonian pyramidal syndrome (PPS), characterized by Parkinsonian symptoms and pyramidal tract signs. The F-box domain has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression.

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                 ....*....|....*....|....*....|....*....|..
gi 302129687 207 LPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTKTGSLWKHLY 248
Cdd:cd22087    4 LPPEIKLRILSLLDVRSLLSLSQVCRDLNSATNDQLLWRFLL 45

F-box domain found in F-box only protein 31 (FBXO31) and similar proteins; FBXO31, also called FBX31, or FBXO14, is a component of an SCF (SKP1-cullin-F-box) protein ligase complex that plays a central role in G1 arrest following DNA damage. It specifically recognizes phosphorylated cyclin-D1 (CCND1), promoting its ubiquitination and degradation by the proteasome, resulting in G1 arrest. FBXO31 may act as a tumor suppressor. The F-box domain has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|..
gi 302129687 204 ITHLPPEVMLSIFSYLNPQELCRCSQVSMKWSQLTKTGSLWK 245
Cdd:cd22102    1 ILDLPPELLVEIFSSLPGTDLPSLAQVCKKFREILNTDTIWQ 42

F-box domain found in the early mitotic inhibitor (EMI) family of F-box proteins; The EMI family includes FBX5 (EMI1) and FBX43 (EMI2), which are anaphase-promoting complex/cyclosome (APC/C) inhibitors that bind APC/C-CCD20 (Cell division cycle protein 20) and/or APC/C-CDH1 (CDC20 homologue 1) complexes. The F-box domain has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression.

                         10        20        30
                 ....*....|....*....|....*....|....
gi 302129687 215 IFSYLNPQELCRCSQVSMKWSQLTKTGSLWKHLY 248
Cdd:cd22086   15 ILSYLSPEDLCRVSCVSKTWRQICLSDPKANRRR 48

Hemerythrin domain [General function prediction only];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 302129687  16 WRMKQLVGLYCDKLSKTNFSNNNDFRALLQslYatFKEF--KMHEQIENEYIIGLLQQRSQTIYNV-------HsdNKLS 86
Cdd:COG3945   15 RRLLAVLEKLLDRLEEGEEVDFELLRDILD--Y--IREFadRCHHPKEEDILFPRLEERGGEAAGPiavllaeH--EQGR 88

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 302129687  87 EMLSLFEKGLKNVKNEyeQLNYAKQLKERLEAFTRDFLPHMKEEEEVFQPMLMEYFTYEELKDI 150
Cdd:COG3945   89 QLTRELEEALEAYLAG--DVVARDELAAALRAYIALLRQHIAKEENVLFPLAERLLSDEDWEEL 150

F-box domain found in F-box/LRR-repeat protein 6 (FBXL6) and similar proteins; FBXL6, also called F-box and leucine-rich repeat protein 6, or F-box protein FBL6 (FBL6A), is the substrate-recognition component of an SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex. The F-box domain has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 302129687 204 ITHLPPEVMLSIFSYLNPQE-----LCRCSQVSMKWSQLTKTGSLWK 245
Cdd:cd22119    1 GQRLPPEILVKIFQFAVATEgavplLCRLSRVCRLWREVALDPSLWT 47

F-box domain found in F-box only proteins FBXO6, FBXO44 and similar proteins; This subfamily includes FBXO6 and FBXO44. FBXO6, also called FBX6, F-box protein that recognizes sugar chains 2 (FBS2), or F-box/G-domain protein 2 (FBG2), is a substrate-recognition component of SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complexes. It is involved in the endoplasmic reticulum-associated degradation pathway (ERAD) for misfolded lumenal proteins, by recognizing and binding sugar chains on unfolded glycoproteins that are retro-translocated into the cytosol and promoting their ubiquitination and subsequent degradation. FBXO6 can recognize and bind denatured glycoproteins, which are modified with not only high-mannose but also complex-type oligosaccharides. It also recognizes sulfated glycans. FBXO6 is involved in DNA damage response by specifically recognizing activated CHEK1 (phosphorylated on 'Ser-345'), promoting its ubiquitination and degradation. FBXO44, also called FBXO6A, FBX44, or F-box/G-domain protein 3 (FBG3), is a substrate-recognition component of an SCF-type E3 ubiquitin ligase complex. It interacts with SKP1 and CUL1. FBXO44 mediates BRCA1 ubiquitination and degradation. The F-box domain has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 302129687 202 TGITHLPPEVMLSIFSYLNPQEL-CRCSQVSMKWSQLTKTGSLWKH------LYPVHWARG--DWY 258
Cdd:cd22168    2 LTISDLPEDVLLEILSLVPARDLiLSCRLVCSRWRDLVDLPTLWKRkcqregFILKDWDGPpkDWK 67

F-box domain found in F-box only protein 42 (FBXO42) and similar proteins; FBXO42, also called FBX42, or just one F-box and Kelch domain-containing protein (JFK), is the substrate-recognition component of an SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex. It specifically recognizes p53/TP53, promoting its ubiquitination and degradation. FBXO42 is also involved in the ubiquitin-proteasome system that may play a role in the pathogenesis of Parkinson's disease (PD). The F-box domain has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression.

                         10        20        30
                 ....*....|....*....|....*....|....*...
gi 302129687 204 ITHLPPEVMLSIFSYLNP-QELCRCSQVSMKWSQLTKT 240
Cdd:cd22110    1 INDLPEEILEYILSYLSPyGDLKSAALVCKRWHRIIKG 38

F-box domain found in Saccharomyces cerevisiae mitochondrial distribution and morphology protein 30 (ScMDM30) and similar proteins; ScMDM30 is an F-box protein required for maintenance of fusion-competent mitochondria in yeast. It is the substrate-recognition component of an SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. ScMDM30 recognizes FZO1 and regulates the amount of FZO1. It acts as a regulatory factor for the mitochondrial fusion machinery and is required for mitochondrial DNA maintenance. The F-box domain has a role in mediating protein-protein interactions in a variety of contexts, such as polyubiquitination, transcription elongation, centromere binding and translational repression.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....
gi 302129687 204 ITHLPPEVMLSIFSYLNPQELCRCSQVSmKWSQLTKTGSLWKHL 247
Cdd:cd22143    2 FDSLPDEILSIIFSHLPQSDLYNLLFVN-KHFYSLALPELWRSI 44